Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota

Abstract

Perturbations to the vaginal microbiota can lead to dysbiosis, including bacterial vaginosis (BV), which affects a large portion of the female population. In a healthy state, the vaginal microbiota is characterized by low diversity and colonization by Lactobacillus spp., whereas in BV, these species are displaced by a highly diverse population of bacteria associated with adverse vaginal health outcomes. Since prebiotic ingestion has been a highly effective approach to invigorate lactobacilli for improved intestinal health, we hypothesized that these compounds could stimulate lactobacilli at the expense of BV organisms to maintain vaginal health. Monocultures of commensal Lactobacillus crispatus, Lactobacillus vaginalis, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus jensenii, and Lactobacillus iners, in addition to BV-associated organisms and Candida albicans, were tested for their ability to utilize a representative group of prebiotics consisting of lactitol, lactulose, raffinose, and oligofructose. The disaccharide lactulose was found to most broadly and specifically stimulate vaginal lactobacilli, including the strongly health-associated species L. crispatus, and importantly, not to stimulate BV organisms or C. albicans. Using freshly collected vaginal samples, we showed that exposure to lactulose promoted commensal Lactobacillus growth and dominance and resulted in healthy acidity partially through lactic acid production. This provides support for further testing of lactulose to prevent dysbiosis and potentially to reduce the need for antimicrobial agents in managing vaginal health.IMPORTANCE Bacterial vaginosis (BV) and other dysbioses of the vaginal microbiota significantly affect the quality of life of millions of women. Antimicrobial therapy is often poorly effective, causes side effects, and does not prevent recurrences. We report one of very few studies that have evaluated how prebiotics—compounds that are selectively fermented by beneficial bacteria such as Lactobacillus spp.—can modulate the vaginal microbiota. We also report use of a novel in vitro polymicrobial model to study the impact of prebiotics on the vaginal microbiota. The identification of prebiotic lactulose as enhancing Lactobacillus growth but not that of BV organisms or Candida albicans has direct application for retention of homeostasis and prevention of vaginal dysbiosis and infection.

Probiotics and prebiotics in intestinal health and disease: from biology to the clinic

“…The extent to which prebiotics can affect microbial communities of the urogenital tract, oral-nasal areas and skin is now the subject of intensive exploration. 7 This Review describes the current understanding of probiotic and prebiotic mechanisms of action, provides important examples of clinical studies on probiotic and prebiotic applications, and discusses current knowledge on mechanisms at the heart of these effects.…”

Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: Implications for in vivo dominance of the vaginal microbiota

“…So strain variability in growth on glycogen (and other carbohydrates) might actually benefit the L. crispatus population as a whole and explain the variation in growth on glycogen that we observed, especially considering that glycogen availability may fluctuate along with oscillating estrogen levels during the menstrual cycle. When developing probiotics, it could thus be beneficial to select for L. crispatus strains that ferment different carbohydrates (in addition to glycogen) [8] and also to supplement the probiotic with a prebiotic [40, 41].…”

“…Total metabolite extracts from spent medium were assessed as previously described by Collins et al . [41]. Biofilm formation was assessed using the crystal violet assay as described by Santos et al .…”

An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps

“…Moreover, prebiotics can be helpful in reducing dermatitis [ 65 ], reducing low density lipoprotein (LDL) in the blood [ 66 ], stimulating the immunological system [ 67 ], increasing iron absorption [ 68 ], maintaining the correct value of intestinal pH [ 69 , 70 ], and alleviating the symptoms of peptic ulcers and vaginal mycosis [ 2 , 71 ]. Other effects of prebiotics such as inulin and oligofructose on human health have been described as being the prevention of carcinogenesis [ 72 , 73 ], the support of lactose intolerance [ 74 ], and the treatment of tooth decay [ 75 ].…”